Search Results (727)

This study investigates the antioxidant properties of aucubin (AU), an iridoid compound, focusing on its ability to scavenge hydroxyl radicals (^•OH) through its hydroxyl functional groups. Gaussian software was employed to model and validate the underlying antioxidant reaction mechanisms. Three primary pathways were examined: hydrogen atom transfer (HAT), sequential electron transfer-proton transfer (SET-PT), and sequential proton loss–electron transfer (SPLET). All calculations were performed using the M06-2X functional within density functional theory (DFT) at the def2-TZVP level, incorporating Grimme’s D3 dispersion correction and the implicit solvation model based on solute electron density (SMD) for water. Various thermodynamic parameters were determined to analyze and compare the antioxidant reactions, including the O-H bond dissociation energy (BDE), ionization potential (IP), proton dissociation enthalpy (PDE), electron transfer enthalpy (ETE), and proton affinity (PA) of the hydroxy groups. The results indicated that the HAT mechanism is the dominant pathway in the scavenging of ^•OH radicals by AU. The key active sites were identified as the 6-OH group in the aglycone structure and the 6′-OH group in the sugar moiety. Moreover, the polar aqueous environment promoted O-H bond homolysis through hydrogen bonding interactions, thereby enhancing the antioxidant activity, and the polar aqueous environment promoted O-H bond homolysis to enhance the antioxidant activity. Full article

N^G, N^G-dimethylarginine (ADMA) is an endogenous compound that acts as a competitive inhibitor of nitric oxide synthase (NOS), thereby reducing nitric oxide (NO) production and contributing to endothelial dysfunction. This dysfunction plays a pivotal role in the development of various pathological conditions, including cardiovascular disease, chronic renal failure, and diabetes. The diminished bioavailability of NO is a critical factor in the progression of these disorders, and alterations in ADMA levels have emerged as significant predictors of cardiovascular events and mortality. In this study, we investigated the molecular characteristics of ADMA using a combined approach of Raman and Fourier Transform Infrared (FT-IR) spectroscopy, complemented by computational simulations with the GaussView 5.0.8 and Gaussian 09 software suite. Experimental Raman and FT-IR spectra were acquired and compared with simulated spectra generated through Density Functional Theory (DFT) calculations. This comparative analysis enabled precise vibrational band assignments and the identification of key molecular vibrational modes, providing valuable insights into ADMA’s structural and vibrational properties. These findings establish a comprehensive spectroscopic reference for ADMA, supporting its potential application as a biomarker in clinical diagnostics. Full article

Atopic dermatitis (AD) is a multifactorial skin disorder characterized by immune and barrier dysfunction. The gut–skin axis is a bidirectional pathway through which gut and skin influence each other via microbial metabolites. Bioactive metabolites produced by microbial transformation of phytochemicals show potential for AD prevention. This study developed a computational systems biology pipeline that prioritized gut-derived metabolites from Philippine medicinal plants by integrating metabolite prediction, pharmacokinetics, network analysis, and molecular simulations. From 2231 predicted metabolites, 31 satisfied pharmacological criteria and were mapped to 199 AD-associated targets, with ALB, CASP3, and PPARG identified as hub genes. Two metabolites, THPOC and PM38, exhibited complementary target affinities and strong binding stability. THPOC stabilized ALB and CASP3, supporting barrier integrity and apoptosis regulation, while PM38 strongly engaged PPARG, modulating lipid metabolism and anti-inflammatory transcription. They exhibited comparable or superior docking scores, stable MD interactions, and favorable binding free energies, compared to abrocitinib, an approved AD treatment. DFT analysis confirmed electronic stability and donor–acceptor properties linked to target selectivity. These findings highlight THPOC and PM38 as promising immunometabolic modulators acting on key AD-related pathways. Collectively, this study introduces a reproducible systems-based computational discovery framework, offering a novel preventive strategy for AD. Full article

In this work, a novel approach for the catalytic reduction of 4-nitrophenol to 4-aminophenol using sodium borohydride is proposed. It was shown that a continuous-flow microreactor system is an optimal tool for PdNP synthesis with dimensions of 3.0 ± 0.5 nm, as well as the performance of catalytic tests with high process efficiency, while keeping a high level of safety. The results obtained from the microreactor system allowed for 100% conversion to 4-aminophenol and were compared to processes carried out in a batch reactor, as well as to a hybrid system which was a combination of a microreactor (synthesis of PdNPs) and batch reactor (catalytic test). These investigations were enhanced by kinetic studies, for which a stopped-flow spectrophotometer was applied due to the extremely high rate of the reaction, i.e., formation of PdNPs (2.1 s), as well as to measure in situ the rate of the heterogeneous catalytic process. To visualize the progress of the heterogeneous reaction more precisely, color coding based on transmittance measurements was employed. Furthermore, to deepen the understanding of the process, a detailed mechanism supported by DFT calculations for the conversion of 4-nitrophenol to 4-aminophenol in the presence of PdNPs was proposed. Full article

This study aims to enhance the oxidative stability of fish oil through encapsulation in pullulan/sodium caseinate (PUL/NaCAS) nanofibers. Electrospinning was employed to produce three formulations: control (0% fish oil) and samples with 5% and 10% fish oil. Characterization of the emulsions showed that increasing oil content led to larger droplet size and reduced viscosity. Scanning electron microscopy (SEM) analysis revealed surface imperfections and a gradual increase in fiber diameter with higher oil loading. Fourier transform infrared (FTIR) spectroscopy confirmed molecular interactions, and fibers with 10% fish oil showed a shift toward a more amorphous structure. Fish oil incorporation also enhanced hydrophobicity and thermal stability, as indicated by thermal and wettability measurements. Antioxidant assays include 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and total phenolic content (TPC), which showed the highest bioactivity at 5% fish oil, with a slight decrease at 10%, likely due to structural saturation. Encapsulation at 5% fish oil significantly reduced lipid oxidation during storage (hydroperoxide values decreased from 8.6 to 4.8 mM at 60 °C/15 days), demonstrating the protective effect of the nanofiber matrix. Docking and density functional theory (DFT) analyses confirmed stable DHA/EPA–caseinate interactions and increased electronic stability, supporting the experimental results. Compared with conventional carriers such as spray-dried or maltodextrin-based systems, PUL/NaCAS nanofibers offered superior oxidative stability, bioactivity, and a biodegradable matrix. Overall, the 80PUL:20NaCAS:5% fish oil formulation represents a versatile platform for stabilizing omega-3 oils, with potential applications in food preservation, nutraceutical delivery, and functional packaging. Full article

Two diphosphonates, etidronic acid (HEDP) and zoledronic acid (ZOL), were radiolabelled with ¹⁶¹Tb and evaluated as potential bone-targeting radiopharmaceuticals. Radiolabeling was performed at pH 7, achieving high radiolabeling yields (greater than 98%) and demonstrating excellent in vitro stability in saline and human serum. Both radiolabeled complexes exhibited hydrophilic behavior, a strong binding affinity to hydroxyapatite, and moderate to high plasma protein binding. Biodistribution studies in healthy Wistar rats demonstrated that ¹⁶¹Tb-HEDP and ¹⁶¹Tb-ZOL achieve high and stable skeletal uptake with rapid blood clearance and minimal soft tissue accumulation. ¹⁶¹Tb-HEDP favored higher initial bone localization, while ¹⁶¹Tb-ZOL showed lower renal and hepatic accumulation, indicating higher safety and selectivity. Compared to unchelated ¹⁶¹TbCl₃, both diphosphonate complexes exhibited significantly higher bone-to-kidney and bone-to-liver ratios, resulting in superior targeting. Complementary experiments with non-radioactive terbium were performed to investigate the redox behavior and confirm complex formation, providing valuable insight into the stability and binding modes of the ligands. Both terbium and the ligands displayed well-defined redox behavior within the potential range of −1 to 1.7 V, with complex formation evidenced by shifts in the oxidation peaks. Density functional theory (DFT) calculations further supported these findings, showing that both phosphonate groups of a ligand coordinate to Tb³⁺, while the hydroxyl groups in HEDP enable intermolecular hydrogen bonding, contributing to additional structural stabilization. Results encourage further investigations of ¹⁶¹Tb-labeled diphosphonates as promising candidates for radionuclide therapy of bone metastases and other skeletal diseases. Full article

Leaching of the extractant from polymer inclusion membranes (PIMs) into the feed and receiving aqueous solutions shortens their life. Therefore, when a particular PIM extractant has been selected, it is important to choose a base polymer that will minimize to the greatest extent extractant leaching compared to other base polymers, thus providing the best stability of the PIM. However, comparisons of the stability of PIMs composed of the same extractant and different base polymers is usually conducted by multiple cycles of extraction and back-extraction steps, which are time-consuming and labor-intensive. An alternative approach based on thermal analysis (thermogravimetric analysis (TGA) and differential thermal analysis (DTA)) was developed and applied to PIMs containing 40 wt.% Aliquat 336, one of the most frequently used PIM extractants, and the three most frequently used PIM base polymers, i.e., poly(vinyl chloride) (PVC), cellulose triacetate (CTA), and poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP). The temperatures and enthalpies associated with Aliquat 336 release were compared, with PVDF-HFP exhibiting the highest values, indicating the strongest interaction between the extractant and the polymer matrix and, thus, the highest stability. The PVC-based PIM was predicted to be the most prone to extractant leaching among the PIMs studied. This stability ranking was confirmed theoretically by quantum chemistry (DFT) calculations, which provided molecular-level insights into the likely interaction sites between Aliquat 336 and the polymer chains. An experimental validation of the above leaching order was also provided by PIM leaching experiments in aqueous 0.1 M and 0.05 M NaCl solutions, where membrane mass losses over a 24 h period were determined. The results of the current study demonstrated thermal analysis to be a fast and viable approach in comparing the stability of PIMs with the same extractant but different base polymers. Full article

Integration of renewable energy into modern power grids remains limited by intermittency and the need for reliable energy storage. Redox flow batteries (RFBs) are promising for large-scale energy storage, yet their widespread adoption is hindered by the high cost. In this study, we investigate isopropanol as a redox-active species with Pt-Cu alloy electrocatalysts for aqueous-organic RFBs. A series of Pt_xCu catalysts with varying Pt:Cu ratios were synthesized and studied for isopropanol electro-oxidation reaction (IPAOR) performance. Among them, PtCu demonstrated the best performance, achieving a low activation energy of 14.4 kJ/mol at 0.45 V vs. RHE and excellent stability at 1 M isopropanol (IPA) concentration. Kinetic analysis and in situ attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy revealed significantly reduced acetone accumulation on PtCu compared to pure Pt, indicating enhanced resistance to catalyst poisoning. Density functional theory (DFT) calculations further identified the first proton-coupled electron transfer (PCET) as the rate-determining step (RDS) with C-H bond scission as the preferred pathway on PtCu. A proof-of-concept PtCu-catalyzed H-cell demonstrated stable cycling over 200 cycles, validating the feasibility of IPA as a low-cost, regenerable redox couple. These findings highlight PtCu-catalyzed IPA/acetone(ACE) chemistry as a promising platform for next-generation aqueous-organic RFBs. Full article

Background/Objectives: Lifitegrast is a recent therapeutic agent provoking scientific and regulatory interest due to its outstanding safety profile and high efficacy in the treatment of dry eye disease. Methods: Herein we employ NMR spectroscopy and mass spectrometry to investigate the weak spots of lifitegrast under standard to extreme stress conditions, resulting in the characterization of three known and nine new degradation products (of which DP7 presented the greatest structural challenge, but was eventually determined as C10 hydroxy derivative, warranting a revision of its previously suggested structure). Results: The first weak spot is identified as a N1–C40 amide bond, and its high susceptibility to hydrolysis is explained through computational DFT analysis. The second and third weak spots are elucidated through bond dissociation energy (BDE) calculations which highlighted the oxidative vulnerabilities of both the piperidine and benzofuran ring. Conclusions: Additionally, two degradation products, observed in initial, extended, and targeted oxidative forced degradation studies, were selected for in silico toxicity assessment and were predicted to have toxicity profiles comparable to or lower than lifitegrast. Full article

With their considerable capacity and structurally favorable characteristics, layered transition metal oxides have become strong contenders for cathode use in sodium-ion batteries (SIBs). Nevertheless, their practical deployment is challenged by pronounced capacity loss, predominantly induced by unstable cathode–electrolyte interphase (CEI) at elevated voltages. In this study, difluoroethylene carbonate (DFEC) is introduced as a functional electrolyte additive to engineer a robust and uniform CEI. The fluorine-enriched CEI effectively suppresses parasitic reactions, mitigates continuous electrolyte decomposition, and facilitates stable Na⁺ transport. Consequently, Na/NaNi_1/3Fe_1/3Mn_1/3O₂ (Na/NFM) cells with 2 wt.% DFEC retain 78.36% of their initial capacity after 200 cycles at 1 C and 4.2 V, demonstrating excellent long-term stability. Density functional theory (DFT) calculations confirm the higher oxidative stability of DFEC compared to conventional solvents, further supporting its interfacial protection role. This work offers valuable insights into electrolyte additive design for high-voltage SIBs and provides a practical route to significantly improve long-term electrochemical performance. Full article

Background: Neuromuscular training is widely implemented in professional football to enhance performance and reduce injury risk. Although unstable surfaces are commonly used for proprioceptive and rehabilitation purposes, limited evidence supports their effectiveness in improving sport-specific force production and stability in elite athletes. This study aimed to compare the effects of multicomponent neuromuscular training performed on stable versus unstable surfaces on unilateral force production, mobility, and agility in elite male soccer players. Methods: Twenty-seven professional male soccer players from the Spanish first division were randomly assigned to either a stable surface group (SSG; n = 14) or an unstable surface group (USG; n = 13). Both groups completed a 10-week intervention in addition to their regular training routines. Pre- and post-intervention assessments included dorsiflexion range of motion (DFt), Y-Balance Test (YBT), single-leg countermovement jump (SLCMJ), single-leg hop for distance (SLH), side-hop (SH), Speedy Jump (SpJ), Agility T-test (TT), and the Lower Extremity Functional Test (LEFT). A two-way repeated-measures ANOVA and Hedges’ g effect sizes were used for statistical analysis. Results: The SSG showed significant improvements in most performance variables, including DFt, YBT, SLH, SH, SpJ, TT, and LEFT (percent change range: 1.6% to 9.8%; Hedges’ g ranging from 0.52 to 2.57). The USG showed limited improvements, with significant changes only in LEFT (percent change = 1.18%; Hedges’ g = 0.53). Notably, the stable surface group demonstrated enhanced force production and agility, particularly in the non-dominant limb. Conclusions: Multicomponent neuromuscular training on stable surfaces appears more effective than training on unstable surfaces for improving unilateral strength, mobility, and agility in elite soccer players. These findings suggest that stable surface training may provide superior performance benefits and should be considered a priority in high-performance environments. Full article

Background/Objectives: Cancer progression is characterized by the suppression of apoptosis, activation of metastatic processes, and dysregulation of cell proliferation. The proper functioning of these mechanisms relies on critical signaling pathways, including Phosphoinositide 3-kinase/Protein kinase B/mammalian Target of Rapamycin (PI3K/Akt/mTOR), Mitogen-Activated Protein Kinase (MAPK), and Signal Transducer and Activator of Transcription 3 (STAT3). Although curcumin and resveratrol exhibit anticancer properties and affect these pathways, their pharmacokinetic limitations, including poor bioavailability and low solubility, restrict their clinical application. The aim of our study was to evaluate the synergistic anticancer potential of curcumin and resveratrol through hybrid molecules rationally designed from these compounds to mitigate their pharmacokinetic limitations. Furthermore, we analyzed the multi-target anticancer effects of these hybrids on the AKT serine/threonine kinase 1 (AKT1), MAPK, and STAT3 pathways using in silico molecular modeling approaches. Methods: Three hybrid molecules, including a long-chain (ELRC-LC) and a short-chain (ELRC-SC) hybrid, an ester-linked hybrid, and an ether-linked hybrid (EtLRC), were designed using the Avogadro software (v1.2.0), and their geometry optimization was carried out using Density Functional Theory (DFT). The electronic properties of the structures were characterized through Frontier Molecular Orbital (FMO), Molecular Electrostatic Potential (MEP), and Fourier Transform Infrared (FTIR) analyses. The binding energies of the hybrid molecules, curcumin, resveratrol, their analogs, and the reference inhibitor were calculated against the AKT1, MAPK, and STAT3 receptors using molecular docking. The stabilities of the best-fitting complexes were evaluated through 100 ns molecular dynamics (MD) simulations, and their binding free energies were estimated using the Molecular Mechanics/Poisson–Boltzmann Surface Area (MM/PBSA) method. Results: DFT analyses demonstrated stable electronic characteristics for the hybrids. Molecular docking analyses revealed that the hybrids exhibited stronger binding compared to curcumin and resveratrol. The binding energy of −11.4 kcal/mol obtained for the ELRC-LC hybrid against AKT1 was particularly remarkable. Analysis of 100 ns MD simulations confirmed the conformational stability of the hybrids. Conclusions: Hybrid molecules have been shown to exert multi-target mechanisms of action on the AKT1, MAPK, and STAT3 pathways, and to represent potential anticancer candidates capable of overcoming pharmacokinetic limitations. Our in silico-based study provides data that will guide future in vitro and in vivo studies. These rationally designed hybrid molecules, owing to their receptor affinity, may serve as de novo hybrid inhibitors. Full article

Hydrogen-bond-like M···H–C interactions in square-planar d⁸ metal complexes have recently gained attention as structure-directing elements and design motifs in asymmetric catalysis. In this study, we explore these weak interactions not as static features, but as key modulators of molecular motion. We synthesized four cis-[N,N′-pentamethylenebis(iminomethylazolato)]M(II) (M = Pt, Pd), including iminomethyl-2-imidazole, iminomethyl-5-imidazole, and iminomethylpyrrolato Pt(II) complexes and an iminomethylpyrrolato Pd(II) analog. All complexes display reversible flipping of the alkylene bridge across the coordination plane, with the M···H–C interaction alternately engaging from above or below. This dynamic motion was characterized by variable-temperature ¹H NMR spectroscopy, revealing activation parameters for the flipping process. X-ray crystallography confirmed geometries consistent with hydrogen-bond-like interactions, while NBO analysis based on DFT calculations provided insight into their electronic nature. Interestingly, although Pt and Pd display comparable M···H–C distances, solvent effects dominate the flipping kinetics over metal identity. These findings highlight the role of hydrogen-bond-like M···H–C interactions not only in structural stabilization, but also in regulating conformational dynamics. Full article

The activation and dissociation of O₂ molecules play a key role in the oxidation of toxic gas molecules and the oxygen reduction reaction (ORR) in hydrogen–oxygen fuel cells. The interactions between O₂ molecules and the surfaces of Fe-doped γ-graphyne were systematically explored, mainly adopting the combined method of the density functional theory with dispersion correction (DFT-D3) and the climbing image nudged elastic band (CI-NEB) method. The order of the formation energy values of these defective systems is E_f(Fe_C2) < E_f(Fe_C1) < E_f(Fe_D1) < E_f(V_C1) < E_f(V_D1) < E_f(V_C2) < E_f(Fe_D2) < E_f(V_D2), which indicates that the process of Fe dopant atoms substituting single-carbon atoms/double-carbon atoms is relatively easier than the formation of vacancy-like defects. The results of ab initio molecular dynamics (AIMD) simulations confirm that the doped systems can maintain structural stability at room temperature conditions. Fe-doped atoms transfer a certain amount of electrons to the adsorbed O₂ molecules, thereby causing an increase in the O-O bond length of the adsorbed O₂ molecules. The electrons obtained by the anti-bonding 2π* orbitals of the adsorbed O₂ molecules are mainly derived from the 3d orbitals of Fe atoms. There is a competitive relationship between the substrate’s carbon atoms and the adsorbed O₂ molecules for the charges transferred from Fe atoms. In the C1 and C2 systems, O₂ molecules have a greater advantage in electron accepting ability compared to the substrate’s carbon atoms. The elongation of O-O bonds and the amount of charge transfer exhibit a positive relationship. More electrons are transferred from Fe-3d orbitals to adsorbed O₂ molecules, occupying the 2π* orbitals of adsorbed O₂ molecules, further elongating the O-O chemical bond until it breaks. The dissociation process of adsorbed O₂ molecules on the surfaces of GY-Fe systems (C2 and D2 sites) involves very low energy barriers (0.016 eV for C2 and 0.12 eV for D2). Thus, our studies may provide useful insights for designing catalyst materials for oxidation reactions and the oxygen reduction reaction. Full article

The applications of electromagnetic (EM) field treatment on water in agriculture have garnered increasing attention as a sustainable method to enhance plant growth, water-use efficiency, and metabolic performance. A growing body of evidence suggests that exposure to EM fields can affect water molecules, possibly by influencing hydrogen bonding dynamics, the structuring of water clusters, and electrokinetic properties of the water molecules. These alterations are thought to correlate with plant physiological performance. The methodology of the study was divided into two parts. The first part focused on the preparation of electromagnetically treated water. The second part involved applying this treated water to spinach plants. The present study investigates the physiological responses of Spinacia oleracea L. to irrigation with electromagnetically treated water (EMTW), focusing on elucidating the potential mechanisms that may underlie the observed effects. EMTW was generated using a solenoid-based system operating in dual-frequency ranges (100–1000 Hz and 10–100 kHz), which has been previously shown to influence both the microbiological and electrokinetic properties of aqueous systems. To evaluate the structural and functional implications of EMTW, a combined methodological approach was employed, integrating proton nuclear magnetic resonance (¹H-NMR) spectroscopy, density functional theory (DFT) modeling of water hydrogen bonds and clusters, and comprehensive plant physiological assessments. Plants were cultivated under both controlled and field conditions to assess consistency across environmental settings. Physiological measurements demonstrated that EMTW irrigation increased photosynthetic rate by ~80%, transpiration by 49–67%, stomatal conductance by 78–129%, intercellular CO₂ concentration by 42–80%, and chlorophyll content by 9.3–9.5% compared to control samples. Additionally, phenoloc and flavonoid contents were elevated by 7.4% and 7.6%, respectively, in field-grown plants. These enhancements were statistically significant (p < 0.001 or p < 0.01) under both laboratory and field conditions, confirming the robustness of the observed effects. Full article